U.S. patent application number 13/539518 was filed with the patent office on 2012-12-27 for ready-to-eat feed for domestic pets.
This patent application is currently assigned to Alzchem Trostberg GmbH. Invention is credited to Thomas Gastner, Hans-Peter Krimmer.
Application Number | 20120329872 13/539518 |
Document ID | / |
Family ID | 38141127 |
Filed Date | 2012-12-27 |
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United States Patent
Application |
20120329872 |
Kind Code |
A1 |
Gastner; Thomas ; et
al. |
December 27, 2012 |
Ready-To-Eat Feed For Domestic Pets
Abstract
A new finished feed for domestic pets is proposed, containing at
least one guanidinoacetic acid component as the active component
with regard to nutritional physiology. The new finished feed which
preferably has a water content of >8% by weight, can be produced
in an extremely economical manner, wherein the main component has a
significantly higher stability during passage through the
gastrointestinal tract and is therefore only converted into
creative under physiological conditions. For this reason the
guanidinoacetic acid is also utilized to a high degree by the
target group which is in particular cats and dogs.
Inventors: |
Gastner; Thomas;
(Engelsberg, DE) ; Krimmer; Hans-Peter;
(Kirchweidach, DE) |
Assignee: |
Alzchem Trostberg GmbH
Trostberg
DE
|
Family ID: |
38141127 |
Appl. No.: |
13/539518 |
Filed: |
July 2, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12281015 |
Nov 18, 2008 |
|
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PCT/EP2007/001783 |
Mar 1, 2007 |
|
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13539518 |
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Current U.S.
Class: |
514/556 ;
514/565 |
Current CPC
Class: |
A23K 20/105 20160501;
A61P 3/02 20180101; A23K 50/42 20160501 |
Class at
Publication: |
514/556 ;
514/565 |
International
Class: |
A61K 31/198 20060101
A61K031/198; A61P 3/02 20060101 A61P003/02; A61K 31/205 20060101
A61K031/205 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 1, 2006 |
DE |
10 2006 009 373.9 |
Claims
1-9. (canceled)
10. A finished feed for domestic pets comprising at least one
guanidinoacetic acid component, wherein said finished feed is
obtained by a process in which said finished feed is industrially
processed after addition of the guanidinoacetic acid component to
other ingredients of the finished feed, wherein said finished feed
is stable when stored, and the guanidinoacetic acid component is
guanidinoacetic acid in a free form, guanidinoacetic acid as a salt
or in a form of an addition or complex compound, which is obtained
with guanidinoacetic acid and one or more of malic acid, aspartic
acid, ascorbic acid, succinic acid, pyruvic acid, fumaric acid,
gluconic acid, a-ketoglutaric acid, oxalic acid, pyroglutamic acid,
3-nicotinic acid, lactic acid, citric acid, maleic acid, sulphuric
acid, acetic acid, formic acid, 2-hydroxybenzoic acid, L-carnitine,
acetyl-L-carnitine, taurine, betaine, choline, methionine, liponic
acid, sodium, potassium or calcium, wherein the guanidinoacetic
acid component is present in the finished feed in an amount of 0.01
to 1% by weight.
11. The finished feed of claim 10, wherein the feed is dry feed,
semi-moist feed or wet feed.
12. The finished feed of claim 11, wherein the feed is in the form
of canned feed, pellets, granulates, biscuits, croquettes, nuggets,
flakes or snacks.
13. The finished feed of claim 11, comprising a water content of
between 8% and 80% by weight.
14. The finished feed of claim 10, wherein the guanidinoacetic acid
component is in a dissolved form.
15. The finished feed of claim 10, further comprising a methyl
group donor.
16. The finished feed of claim 18, wherein the methyl donor is
choline, betaine, or a combination thereof
17. The finished feed of claim 10, wherein the domestic pet is a
carnivore.
18. The finished feed of claim 17, wherein the carnivore is a cat
or a dog.
19. A method of providing nutrition to a domestic pet comprising:
administering to the domestic pet a finished feed comprising at
least one guanidinoacetic acid component, wherein said finished
feed is obtained by a process in which said finished feed is
industrially processed after addition of the guanidinoacetic acid
component to other ingredients of the finished feed, wherein said
finished feed is stable when stored, and the guanidinoacetic acid
component is guanidinoacetic acid in a free form, guanidinoacetic
acid as a salt or in a form of an addition or complex compound,
which is obtained with guanidinoacetic acid and one or more of
malic acid, aspartic acid, ascorbic acid, succinic acid, pyruvic
acid, fumaric acid, gluconic acid, .alpha.-ketoglutaric acid,
oxalic acid, pyroglutamic acid, 3-nicotinic acid, lactic acid,
citric acid, maleic acid, sulphuric acid, acetic acid, formic acid,
2-hydroxybenzoic acid, L-carnitine, acetyl-L-carnitine, taurine,
betaine, choline, methionine, liponic acid, sodium, potassium or
calcium, wherein the guanidinoacetic acid component is present in
an amount of 0.01 to 1% by weight.
20. The method of claim 19, wherein the domestic pet is a
carnivore.
21. The method of claim 20, wherein the carnivore is a cat or a
dog.
22. A method of making a finished feed for domestic pets
comprising: providing ingredients of the finished feed; obtaining a
guanidinoacetic acid component; mixing the guanidinoacetic acid
component with the ingredients to form a mixture; and industrially
processing the mixture to make the finished feed, wherein the
guanidinoacetic acid component is present in the finished feed in
an amount of 0.01 to 1% by weight.
23. The method of claim 22, wherein said guanidinoacetic acid
component is guanidinoacetic acid in a free form, guanidinoacetic
acid as a salt or in a form of an addition or complex compound,
which is obtained with guanidinoacetic acid and one or more of
malic acid, aspartic acid, ascorbic acid, succinic acid, pyruvic
acid, fumaric acid, gluconic acid, .alpha.-ketoglutaric acid,
oxalic acid, pyroglutamic acid, 3-nicotinic acid, lactic acid,
citric acid, maleic acid, sulphuric acid, acetic acid, formic acid,
2-hydroxybenzoic acid, L-carnitine, acetyl-L-carnitine, taurine,
betaine, choline, methionine, liponic acid, sodium, potassium or
calcium.
24. The method of claim 22, wherein industrially processing the
mixture comprises heating the mixture to about 160.degree. C. and
extruding the heated mixture.
25. A method of providing nutrition to a domestic pet comprising:
administering to the domestic pet a finished feed comprising at
least one guanidinoacetic acid component, wherein said finished
feed is obtained by a process in which said finished feed is
industrially processed after addition of the guanidinoacetic acid
component to other ingredients of the finished feed, wherein said
finished feed is stable when stored, and the guanidinoacetic acid
component is guanidinoacetic acid in a free form, guanidinoacetic
acid as a salt or in a form of an addition or complex compound,
which is obtained with guanidinoacetic acid and one or more of
malic acid, aspartic acid, ascorbic acid, succinic acid, pyruvic
acid, fumaric acid, gluconic acid, .alpha.-ketoglutaric acid,
oxalic acid, pyroglutamic acid, 3-nicotinic acid, lactic acid,
citric acid, maleic acid, sulphuric acid, acetic acid, formic acid,
2-hydroxybenzoic acid, L-carnitine, acetyl-L-carnitine, taurine,
betaine, choline, methionine, liponic acid, sodium, potassium or
calcium.
26. A method of making a finished feed for domestic pets
comprising: providing ingredients of the finished feed; obtaining a
guanidinoacetic acid component; mixing the guanidinoacetic acid
component with the ingredients to form a mixture; and industrially
processing the mixture to make the finished feed.
Description
PRIOR RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 12/281,015 filed Nov. 18, 2008, which is a
national phase of PCT/EP2007/001783 filed Mar. 1, 2007, which
claims the benefit of priority to DE 10 2006 009 373.9 filed Mar.
1, 2006, each of which is incorporated by reference herein in its
entirety.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] FIG. 1. Content of creatine and guanidinoacetic acid in
water at pH 7 following exposure to 160.degree. C. for 30 minutes.
Guanidinoacetic acid has significantly higher stability than
creatine.
[0003] FIG. 2. Content of creatine and guanidinoacetic acid in
water at pH 5 over 60 days. Guanidinoacetic acid has significantly
higher storage stability than creatine.
DESCRIPTION
[0004] The present invention concerns a finished feed for domestic
pets which contains a guanidinoacetic acid component as the active
component in terms of nutritional physiology.
[0005] Guanidinoacetic acid (GAA) is an endogenous substance which
occurs in animals and also in humans and plays a central role in
the biosynthesis of creatine. Creatine can be assimilated from food
and also be formed endogenously. The biosynthesis starts from
glycine and L-arginine. In mammals the guanidino group of
L-arginine is cleaved and an N-C-N group is transferred to glycine
by the enzyme aminotransferase primarily in the kidneys but also in
the liver and pancreas. L-arginine is converted into L-ornithine in
this process. The guanidinoacetic acid that is formed in this
manner is converted in the next step into creatine with the aid of
the enzyme transmethylase which occurs exclusively in the liver in
the case of vertebrates. In this process S-adenosyl methionine
serves as a methyl group donor. The creatine is subsequently
transported via the blood circulation to the target organs. It is
transported through the cell membrane into the cells by a specific
creatine transporter.
[0006] Several working groups have already shown in clinical
studies in the fifties of the last century that the administration
of guanidinoacetic acid in combination with betaine has a positive
effect on the course of the disease in the case of cardiac
diseases. The patients reported a considerable improvement in their
general state of health. In addition an improved endurance during
physical exercise and increased muscle strength were already found
after a short treatment period. The patients also reported an
improved libido. 200 patients were administered a dose of 30 mg
GAA/kg daily for one year. Side effects were not observed (Borsook
H.; Borsook M. E.: The biochemical basis of betaine-glycocyamine
therapy. In Annals of western medicine and surgery 5(10), 825,
1951).
[0007] The International Patent Application WO 91/07954 A1
discloses the use of guanidinoacetic acid in combination with
methionine or S-adenosyl methionine to increase the creatine level
in the muscle. Conditions were mentioned as a field of application
which require an increased creatine level in the muscle. Medical
applications as well as the field of sport nutrition are
claimed.
[0008] In this connection it is asserted that the administration of
creative does not increase the creatine level. This assertion has
now been disproven by numerous publications (e.g. Persky, A. M.,
Brazeau, G. A.: Clinical Pharmacology of the Dietary Supplement
Creatine Monohydrate. In: Pharmacol. Rev. 2001, 53, 161-176). A
direct comparison of the efficacy of creatine and guanidinoacetic
acid is not disclosed in WO 91/07954.
[0009] It is also known that guanidinoacetic acid has an
antibacterial action and has been successfully used against
bacterial infections (Staphylococcus aureus) in animal experiments
(Preparation for protecting mammals against infection, Stanley Drug
Products Inc. USA; Neth. Appl. (1976), 7 pp. NL 7411216).
[0010] In connection with the overdosing of methionine it is also
known that the associated negative effects can be attenuated by the
administration of guanidinoacetic acid (Interrelations of choline
and methionine in growth and the action of betaine in replacing
them. McKittrick, D. S., Univ. of California, Berkeley, Archives of
Biochemistry (1947), 15, 133-155).
[0011] The International Patent Application WO 2004/000297 A1
describes a mixture for feeding or pharmaceutical purposes in
mammals. This mixture consists of a protein fraction which contains
L-serine and guanidinoacetic acid as a further component. The
mixture should in this connection be free from glycine or, after
hydrolysis of the mixture, it should contain a ratio of L-serine to
glycine of more than 2.7:1. Solutions, emulsions, suspensions,
gels, bars, sweets and preferably powder are mentioned as possible
forms of the product. There is no mention of the use of
guanidinoacetic acid as a finished feed for domestic animals.
[0012] A ratio of L-serine to glycine of more than 2.7:1 is not
encountered in commercially available pet food for domestic pets.
Raw materials from animals such as e.g. meat and bone meal contain
considerably more glycine than serine (Amino acids of meals of
animal origin; de Vuyst, A. Univ. Louvain, Belgium, Agricultura
(Heverlee, Belgium) (1964), 12(1), 141-151). In plant raw materials
the ratio between glycine and serine is predominantly balanced.
[0013] Creatine plays an important role in the energy metabolism of
the cell where in addition to adenosine triphosphate (ATP), it
represents an important energy reserve of the muscle in the fowl of
energy-rich phosphocreatine. In the resting state of the muscle ATP
can transfer a phosphate group onto creatine to form
phosphocreatine which is then in direct equilibrium with ATP.
During muscle work it is very important to fill up the ATP stores
again as rapidly as possible. Phosphocreatine is available for this
purpose in the first seconds of maximum muscle load. A phosphate
group can be transferred from phosphocreatine onto adenosine
diphosphate by the enzyme creatine kinase in a very rapid reaction
and thus regenerate ATP. This is also referred to as the Lohmann
reaction.
[0014] Creatine has been known for a long time as a suitable food
supplement and animal feed. The creatine stores that are naturally
present in the body are rapidly exhausted during intense and
prolonged muscle work. Targeted administration of creatine has a
positive effect on the endurance and performance especially in
competitive athletes where undesired accumulation processes in the
body or disadvantageous degradation products are unknown. The
reason for this is because if creatine is fed in excess, it is
eliminated from the body as creatine and creatiniue.
[0015] Furthermore, it is known that a creatine supplementation
results in an increase of body mass. This is initially due to an
increased uptake of water into the muscle. However, in the
long-term creatine indirectly results in an increase in muscle mass
due to increased protein synthesis or a reduced protein catabolism
in the myofibrils. (Int. J. Sports Med. 21 (2000), 139-145). Thus,
the result is an increased fat-free body mass.
[0016] In addition to creatine itself i.e. creatine monohydrate,
numerous creatine salts such as creatine ascorbate, citrate,
pyruvate and others have in the meantime also proven to be suitable
food supplements. At this point the European Patent EP 894 083 B1
and the German laid-open patent application DE 197 07 694 A1 are
mentioned as representatives.
[0017] The proven positive effects in humans are also displayed by
creatine in animals which is why its use in diverse animal feeds is
also sufficiently previously described. Studies on dogs were
already carried out by Benedict and Osterberg in 1923. It was
observed that creatine administered orally at a daily dose of about
40 mg/kg for several weeks results in a considerable increase in
weight. A positive nitrogen balance was also observed (The Journal
of Biological Chemistry No. 1 (1923), 229-252).
[0018] GB 2 300 103 teaches the use of creatine in the form of a
dog biscuit for which purpose creatine monohydrate is offered
together with meat in an extruded paste.
[0019] The use of creatine or creatine salts as a feed additive for
breeding animals and fattened animals, as a substitute for meat and
bone meal, fish meal and/or antimicrobial performance enhancers,
growth hormones and anabolics has been previously described in the
International Patent Application WO 00/67 590 A1.
[0020] Since creatine monohydrate is insufficiently bioavailable
due to its poor solubility, it is recommended that is should be
used together with other physiologically active compounds
preferably in a salt form. The German laid-open specification DE
198 450 A1 concerns the use of stable pyruvic acid salts in
particular of creatine pyruvate in formulations which are suitable
for animal feeds.
[0021] Creatine is a natural component in the diet of carnivorous
and omnivorous wild animals. Thus wolves which have a body weight
between 15 and 60 kg eat on average 100-130 g meat per kilogram
body weight per day. Fresh meat contains between 3 and 6 g (23-46
mmol) creatine per kilogram. Thus, a wolf of 35 kg takes in about
3.5 to 4.5 kg fresh meat which contains between 10.5 and 27 g
creatine. In contrast about 1.25 kg meat is sufficient for
domesticated dogs with a body weight of 35 kg. If it is ingested in
a fresh and raw form, it contains between 3.75 and 7.5 g creatine
(Research in Veterinary Science 62 (1997), 58-62).
[0022] In addition to its undisputed positive physiological
properties, creatine, however, also has the disadvantage that it is
very unstable in aqueous solutions and moist formulations
especially at high temperatures where it is converted into
creatinine. Commercially produced animal feed is heated strongly
during processing to make it stable. Thus, for example in the
production of dry dog and cat biscuits, the raw materials are
heated in extruders to temperatures of up to 190.degree. C.
Humidity, pressure and heat gelatinize the starch that is present
and the paste that is obtained is subsequently brought into the
desired form. The high temperatures during processing and the
storage under moist conditions such as for example in canned food
which contains about 75-85% water has the effect that most of the
creatine that it contains is converted into creatinine. This was
also demonstrated by Harris in commercial canned food and dry food
for dogs. The examined eight canned foods only contained traces of
creatine (0.36 to 1.93 mmol/kg). Also in dry feeds values of 0.7
mmol creatine per kilogram were measured in most of the samples
(Research in Veterinary Science 62 (1997), 58-62). Thus, it is
apparent that dogs and cats which are fed with commercial animal
feeds (0.36-4.25 mmol creatine per kilogram feeding stuff) ingest
considerably less creatine via the food than would be the case with
a natural diet with fresh meat (23-46 mmol creatine per
kilogram).
[0023] This instability of creatine is also important with respect
to oral ingestion. The pH of the stomach of 1 to 2 can result in a
considerable degradation of creatine to creatinine depending on the
retention time. Thus, in humans it was shown that after an oral
administration of creatine, only about 15 to 30% could be
reabsorbed by the muscle (Greenhaff, P. L.: Factors Modifying
Creatine Accumulation in Human Skeletal Muscle. In: Creatine. From
Basic Science to Clinical Application. Medical Science Symposia
Series Volume 14, 2000, 75-82).
[0024] From the described disadvantages of the state of the art
with regard to creatine, the object of the present invention was to
find compounds for finished feeds which, if possible, have a low
instability in industrial processing processes. They should not
only withstand high processing temperatures without damage, but
should also be stable when stored for example in canned feeds under
moist conditions. Furthermore, the compound, in contrast to
creatine, should survive the acidic environment of the stomach
without damage and not be converted into creatine until it has been
taken up into the body. The feed additives that are used should
themselves display no physiologically disadvantageous effects and
should be easy to detect. From an economic point of view it is
important that the substances that are used according to the
invention can be produced in an economically favourable manner.
[0025] This object was achieved by finished feeds for domestic pets
which contain guanidinoacetic acid and/or guanidinoacetic acid
salts as the active component with regard to nutritional
physiology.
[0026] In finished feeds it was surprisingly found that the
guanidinoacetic acid components do in fact fulfill the requirement
profile according to the object because they can be produced in a
simple and economic manner; in contrast to creatine or creatine
monohydrate, guanidinoacetic acid and salts thereof have a
considerably higher stability in acidic solutions such as those
that occur in the stomach and they are only converted into creatine
under physiological conditions. Surprisingly it has turned out to
be particularly advantageous that in contrast to creatine,
guanidinoacetic acid and salts thereof described in the present
connection are thus not converted until after they have been
reabsorbed which occurs primarily in the liver. Thus, in contrast
to the known creatine most of the compounds used are not already
degraded in advance by instability reactions and eliminated, but
are in fact made available to the physiological fields of
application. Thus, according to the invention guanidinoacetic acid
and salts thereof can be used in considerably lower dosages
compared to creatine, while having an identical effect.
[0027] Furthermore, it was possible to show that guanidinoacetic
acid has a very high stability under conditions such as those which
occur during the industrial production of feedstuffs. In this
connection guanidinoacetic acid exhibits clear advantages over
creatine. In addition it was possible to show that guanidinoacetic
acid has a considerably better storage stability than creatine.
These advantages were thus in their entirety not predictable.
[0028] Due to the surprisingly favourable properties of the
guanidinoacetic acid component in the claimed finished feed, it is
not limited to specific forms of administration. But rather
variants in the form of dry, semi-moist and wet feeds come equally
into consideration such as in particular canned feeds, pellets,
granulates, biscuits, croquettes, nuggets, flakes and snacks which
is also taken into consideration by the present invention.
[0029] The finished feed is preferably based on animal or/and plant
raw materials. Furthermore, the finished feed preferably contains
glycine. The finished feed preferably contains glycine in a ratio
to L-serine of more than 1:2.7, preferably of 1:1 or more after
hydrolysis.
[0030] As already mentioned the finished feed according to the
invention is surprisingly stable in storage although it can also
have high contents of water. The proposed finished feed should
preferably have a water content of >8% by weight, where water
contents above 10% by weight and in particular in the range between
20 and 80% by weight are preferred.
[0031] The guanidinoacetic acid component according to the
invention can, according to the invention, not only be present in a
free form i.e. actually as guanidinoacetic acid but also as a salt
or in the form of an addition or complex compound. Of course all
mixed forms of these compound types are also possible.
[0032] Guanidinoacetic acid salts have proven to be favourable for
the finished feed according to the invention which are obtained
with aspartic acid, ascorbic acid, pyruvic acid, succinic acid,
fumaric acid, gluconic acid, oxalic acid, pyroglutamic acid,
3-nicotinic acid, lactic acid, citric acid, maleic acid, sulphuric
acid, formic acid, hydrochloric acid and phosphoric acid, where
potassium, calcium or sodium guanidinoacetate are particularly
suitable. Of course mixtures of guanidinoacetic acid with one or
more of the above-mentioned salts can also be used or mixtures
which consist of the above-mentioned salts.
[0033] As another advantage it has turned out that guanidinoacetic
acid and salts thereof can be used in the finished feed in a
relatively wide quantity range. Based on the total finished feed it
should contain the guanidinoacetic acid component preferably in
amounts of 0.01 to 20% by weight, in particular in amounts of 0.1
to 1.0% by weight and particularly preferably in an amount of 0.2
to 0.5% by weight.
[0034] Of course in addition to the guanidinoacetic acid component
the finished feed can also contain other ingredients such as for
example components that are also active with regard to nutritional
physiology and/or formulation auxiliaries or fillers.
[0035] In this case it may indeed be advisable depending on the
respective specific application case to add methyl group donors
such as choline, betaine and/or methionine as additional
physiologically-active components.
[0036] Overall the present invention finds new uses for
guanidinoacetic acid and its salts in the diet especially of
carnivores such as dogs and cats where they have considerable and
surprising advantages compared to the previously known creatine
compounds.
[0037] The following examples illustrate the breadth of the present
invention.
Examples
Example 1
[0038] A mixture consisting of 5000 mg guanidinoacetic acid and
5000 mg betaine was incorporated in the production of 1 kg of a
commercial soft feed for dogs. The amount of guanidinoacetic acid
in the final product was 0.5% by weight.
Example 2
[0039] A formulation consisting of 2500 mg guanidinoacetic acid and
5000 mg betaine was incorporated in 1 kg of a typical formulation
for canned dog food. The amount of guanidinoacetic acid in the
final product was 0.25% by weight.
[0040] Example 3
[0041] A formulation consisting of 2000 mg guanidinoacetic acid
lactate, 750 mg carnitine tartrate, 100 mg sucrose stearate, 160 mg
talcum and 1090 mg fructose was incorporated in 1 kg of a base
paste for dog biscuits. The amount of guanidinoacetic acid in the
final product was 0.2% by weight.
[0042] Example 4
[0043] The following formulation was incorporated homogeneously in
1 kg of a commercial canned cat food mixture as a master batch:
1000 mg guanidinoacetic acid, 400 mg methionine, 2000 mg choline,
40 mg magnesium stearate, 25 mg carboxymethyl cellulose and 135 mg
lactose. The amount of guanidinoacetic acid in the final product
was 0.1% by weight.
Example 5
Stability
[0044] 5.1
[0045] The stability of creatine and guanidinoacetic acid was
compared under conditions which occur when producing industrially
manufactured finished feeds. For this purpose a model system was
used for the extrusion of a moist feed paste at 160.degree. C.
Guanidinoacetic acid and creatine were dissolved in water (pH 7)
and heated in an autoclave for 30 minutes to 160.degree. C.
Subsequently the content of creatine and guanidinoacetic acid was
determined. The rate of the cyclization reaction of creatine to
creatinine and of guanidinoacetic acid to glycocyamidine is only
dependent on the pH and temperature but completely independent of
the concentration.
[0046] The result of the experiment is shown in FIG. 1. This shows
that guanidinoacetic acid has a significantly higher stability than
creatine under the conditions of animal feed production. Whereas
the creatine content is less than 20% of the original content after
30 minutes at 160.degree. C., more than 80% of the guanidinoacetic
acid is still present under the same conditions.
[0047] 5.2
[0048] The stability of creatine and guanidinoacetic acid was
examined in water at pH 5. These conditions are comparable to
storage in canned feeds (75-85% water content). The results are
shown in FIG. 2. It can be seen that guanidinoacetic acid has a
considerably better storage stability than creatine. Whereas no
degradation of guanidinoacetic acid is observed after 60 days, only
87% of the creatine is recovered.
* * * * *